Laboratory Evaluation of Bone Marrow

Etiology and Epidemiology

Bone marrow examination is indicated in a range of clinical scenarios, including the following:

• Unexplained cytosis, cytopenias, or atypical cells on PBS
• Diagnosing and staging of hematopoietic neoplasms
• Evaluation of radiologically detected osseous lesions concerning for metastases
• Investigating hepatosplenomegaly of unknown origin
• Pyrexia of unknown origin, especially when infection or occult hematologic disease is suspected
• Assessment of storage disorders, including glycogen storage disorders and iron deposition [2]

Specimen Requirements and Procedure

The iliac crest is the primary site for obtaining bone marrow specimens. The specimen collection should include BMA, bone marrow cores for trephine biopsy, and blood clots following biopsy. Following the guidelines established by the College of American Pathologists (CAP) and the International Society of Laboratory Hematology (ISLH) helps ensure specimen reporting consistency and accuracy.[3][4]

Testing Procedures

Bone marrow specimen collection for evaluation typically involves 2 procedures: bone marrow aspiration (BMA) and bone marrow biopsy (BMB). These procedures are typically performed in an outpatient setting and are generally well-tolerated. BMA involves using a thin needle to withdraw a liquid bone marrow sample from the posterior iliac crest or, less commonly, sternum or other bones. BMB involves using a larger needle to obtain a solid core sample of bone marrow tissue along with a thin core of bone.

A complete bone marrow laboratory examination requires different specimen types to yield complementary results. These specimen types include the following:

Bone Marrow Aspirates

The World Health Organization (WHO) recommends immediate bedside preparation of aspirate smears using the pull technique or crush film smear to reduce drying artifacts from the initial specimen obtained.[5] Aspirates for flow cytometry should be collected separately in sodium heparin tubes. In contrast, aspirates for molecular studies should be collected in ethylenediaminetetraacetic acid (EDTA) or sodium heparin tubes. Romanoswky stains such as Wright or Giemsa must be used on the aspirates before methanol preservation for ancillary studies. Beyond 2 hours, EDTA-fixed aspirates lose their original morphology and become less suitable for evaluating morphologic dysplasia.[6]

Bone Marrow Cores for Trephine Biopsy

Core biopsy specimens are best obtained after BMA to prevent aspirate contamination with peripheral blood. The same skin entry site may be used, though the aspiration area should be avoided. Imprint smears are obtained by touching the core biopsy specimens onto glass slides. These imprints are especially helpful when aspiration yields a dry tap, and quick preliminary staining is needed after the biopsy procedure.

The most common fixative used during core biopsy sampling is neutral buffered formalin. Zinc formaldehyde and Bouin’s fixative are good alternatives. Calcium salts can make tissues hard and brittle, making sectioning and staining difficult. Decalcification is thus necessary. EDTA is the preferred decalcification agent, as it can preserve nuclear acids for immunohistochemical staining. However, urgent cases, ie, needing a 6-hour decalcification time, require the Hammersmith protocol using 10% formic acid and 5% formaldehyde.[7]

Post-Biopsy Blood Clot

Clots obtained after trephine biopsy may provide additional insights. These clots are fixed in formalin and processed similarly to trephine biopsy specimens. Blood clots help assess marrow cellularity, cellular morphology, and atypical infiltrates, enabling immunohistochemical staining. As decalcification is not required, these samples are better suited for cytogenetics, FISH, and molecular testing. However, flow cytometric analysis cannot be performed on clot samples.

Results, Reporting, and Critical Findings

BMA and BMB are often performed together to provide complementary information about the bone marrow's cellular composition and architecture. Below is a systematic approach to examining marrow aspirates and biopsies for a thorough bone marrow evaluation.

Bone Marrow Aspirate Analysis

Bone marrow aspirate is better suited for assessing cytomorphology, differential cell counts, and performing ancillary studies like flow cytometry, cytogenetics, and molecular testing. A stepwise approach to examining bone marrow aspirates is discussed below.

Low-power magnification

Low-power lenses typically provide 10 times object magnification. The adequacy and overall cellularity of the bone marrow can be appreciated in this setting.

• Adequacy: An adequate bone marrow smear is characterized by numerous particles with trails of cytomorphologically well-defined and well-stained blood cells. The presence of megakaryocytes indicates a successful marrow tap. However, the tap is considered dilute if megakaryocytes are present without particles. In contrast, smears with stromal fragments lacking particles, megakaryocytes, and hematopoietic marrow elements are deemed inadequate and noted as “peripheral blood” or “bloody tap” on the report (see Image. Stromal Fragments).

• Cellular clusters: Metastatic carcinomas and benign marrow cells like plasma cells, osteoblasts, and macrophages can cluster in marrow aspirates. Identifying and further examining these clusters under high-power magnification allows for a detailed analysis of their cytologic features and accurate identification of specific cell types. 

High-power magnification

High-power lenses have a magnifying ability of at least 40 times. High-power magnification is ideal for assessing finer cellular morphological details, including nuclear-cytoplasmic ratio, chromatin pattern, and the presence of any abnormal inclusions, cytoplasmic granules, or parasites. High-power magnification is essential for identifying specific cell types, assessing cell maturation, and detecting morphologic dysplasia and abnormal cells like blasts.

• Cellularity: "Cellularity" refers to the proportion of different cell types present in a bone marrow aspirate. CAP recommends conducting a differential count of 500 cells. However, research suggests that a count of 300 cells may also suffice.[8] The differential cell count includes myeloid (granulocytic and monocytic cells) and erythroid progenitors, lymphoid elements, and plasma cells. Megakaryocytes, histiocytes, mast cells, and nonhematopoietic cells are excluded from this count. A normal myeloid-erythroid ratio falls between 2:1 and 4:1, but this ratio must be interpreted alongside PBS findings for a comprehensive assessment.

• Maturation: Cell maturation in the bone marrow is a continuous process. Increased immature cells, including blasts and blast equivalents such as promyelocytes and promonocytes, suggest a neoplastic process and warrant further investigation (see Image. Bone Marrow Aspirate with Blasts). Acute leukemias are defined by more than 20% blasts or blast equivalents in the bone marrow in the absence of leukemia-defining genetic abnormalities. If the blast count is less than 20%, WHO 2022 guidelines recommend that acute myeloid leukemia (AML) can be diagnosed if defined molecular aberrations accompany this finding. Different AML subtypes have differing morphologic features, immunophenotypes, and prognoses (see Table. Features of Genetically Defined AML).[9] Despite well-defined molecular characteristics, certain AML subtypes with BCR-ABL1 fusion and CEBPA mutation still require more than 20% blasts for diagnosis. Although the boundaries between myelodysplastic neoplasms (MDS) and AML have softened, retaining a blast cutoff of 20% prevents overtreatment.[10][11]

Table 1. Features of Genetically Defined AML

Dysplasia

Erythroid dysplasia is characterized by morphological abnormalities, including nuclear budding and lobation, internuclear bridges, karyorrhexis, binuclear and multinuclearity, cytoplasmic vacuolation, and megaloblastic changes, and the presence of ringed sideroblasts (see Image. Nuclear Budding).[12] Nonneoplastic conditions like megaloblastic anemia, congenital dyserythropoietic anemia, copper deficiency, and zinc excess may also exhibit features of erythroid dysplasia. Ringed sideroblasts may be detected by iron-staining aspirate smears with particles. A semiquantitative score of 1 to 4 is used to evaluate the abundance of ringed sideroblasts. 

Granulocytic dysplasia’s morphologic features include nuclear hypersegmentation and hyposegmentation (pseudo-Pelger-Huët neutrophils), decreased cytoplasmic granularity, Döhle bodies, and Auer rods.[13] Nonneoplastic conditions, including vitamin B12 and folic acid deficiency, hepatitis C and human immunodeficiency virus (HIV) infection, autoimmune diseases like systemic lupus erythematosus, medications like granulocyte macrophage-colony stimulating factor, and hereditary Pelger-Huët anomaly can show morphologic features of granulocytic dysplasia. Using EDTA as an anticoagulant—which lavender-top tubes contain—can give rise to pseudo-dysplastic granulocytes but erythroid dyspoiesis.[14] 

Megakaryocytic dysplasia manifests with micromegakaryocytosis and megakaryocyte hypolobation, multinucleation, and clustering (aggregates with >6 megakaryocytes)(see Images. Dysplastic Megakaryocytes and Dysplastic Megakaryocytes, Hyperlobated). Neoplastic causes of megakaryocytic dysplasia include myeloproliferative neoplasms (MPN), myelodysplastic neoplasms (MDS), and MDS/MPN.

Importantly, nonneoplastic causes should be ruled out in cases presenting with erythroid or granulocytic dysplasia before making a diagnosis of MDS. The dysplasia evaluation includes a comprehensive approach, starting with a detailed clinical history, CBC to assess for cytopenias, PBS examination, and biochemical and serological tests, including vitamin and serologic markers. Further investigations include a bone marrow examination, flow cytometry, cytogenetics, and molecular tests.

In the 5th edition of WHO’s 2022 myelodysplastic neoplasm classification, the term "myelodysplastic neoplasms" has replaced "myelodysplastic syndromes" while retaining the “MDS” abbreviation, aligning the nomenclature with myeloproliferative neoplasms for consistency. Lineage dysplasia can be progressive, indicating disease evolution. Distinguishing between unilineage and multilineage dysplasia is now optional.

Accurate blast percentage determination in bone marrow and peripheral blood helps distinguish between various morphologically defined MDS subgroups. According to the WHO 2022 guidelines, MDS with specific genetic abnormalities are classified as follows:

• MDS with low blasts and isolated del(5q): blasts <5% in the bone marrow and <2% in the peripheral blood
• MDS with low blasts and SF3B1 mutation: blasts <5% in the bone marrow and <2% in the peripheral blood; the presence of >15% ringed sideroblasts obviates the need to find an SF3B1 mutation
• MDS with bi-allelic TP53 inactivation: <20% in bone marrow and peripheral blood

A summary of morphologically defined MDS subgroups is provided below (see Table. Morphologically Defined MDS).[15]

 Table 2. Morphologically Defined MDS

Lymphoma

Bone marrow examination is routinely used to stage lymphoid neoplasms. The presence of cells with blastoid morphology in the background of marrow lymphoglandular bodies should raise the possibility of lymphoma rather than a myeloid neoplasm.[16]

Plasma cell neoplasms

According to the WHO 2022 guidelines, multiple myeloma is diagnosed when at least 10% of clonal plasma cells are detected in the bone marrow, accompanied by one or more myeloma-defining events. These events include clonal bone marrow plasmacytosis exceeding 60%, a serum-free light chain ratio of at least 100, or more than 1 focal lesion on imaging (see Image. Bone Marrow Aspirate with Plasma Cells). Cytogenetic marrow aspirate evaluation is used for myeloma risk stratification. High-risk multiple myelomas are identified by the presence of t(14;16), t(14;20), t(4;14), del(17p), gain(1q), or p53 mutation. Myelomas with 2 or 3 of these high-risk cytogenetics are categorized as double- or triple-hit myelomas, respectively.[17] 

Significance of other cell types

Mast cells may occasionally be observed in bone marrow aspirates and are discussed further below. Macrophages, usually rare, are primarily associated with erythroid islands and may contain hemosiderin.[18] Increasing macrophages might indicate hemolytic anemias, inflammatory conditions, or neoplastic disorders such as myeloproliferative neoplasms.[19] Erythrophagocytosis can be observed in immune hemolysis, hemophagocytic lymphohistiocytosis, and histiocytic neoplasms (see Image. Eyrthrophagocytosis). In lysosomal storage disorders like Gaucher disease, macrophages can accumulate lysosomal products, leading to a distinctive ''wrinkled tissue paper'' appearance.[20]

Bone Marrow Biopsy

Bone marrow trephine biopsy helps assess overall marrow cellularity and architecture, which are especially sensitive in detecting focal lesions. Core biopsy provides better insight into the relationship of bone marrow elements to each other.[21] Below is a systematic approach for evaluating both marrow aspirates and biopsies for a thorough bone marrow evaluation.

Marrow cellularity

Bone marrow cellularity indicates the proportion of hematopoietic elements to both hematopoietic and mature adipose tissue. This value decreases with age. Neonatal marrows are highly cellular (90-100%), declining to 50% by age 30 and further diminishing to 30% by age 70. Subcortical bone marrow is physiologically hypocellular and not optimal for evaluating cellularity.[22]

The correlation between trephine biopsy specimen and bone marrow aspirate cellularity is essential, as a hypercellular aspirate with unremarkable biopsy warrants further investigation. Conversely, a dry tap may indicate marrow fibrosis or infiltration, which is better appreciated on trephine biopsy. 

Cellular distribution

The distribution of maturing hematopoietic elements is better discerned in trephine biopsy sections. Erythroid cells typically cluster in the interstitium. Meanwhile, immature myeloid precursors reside in the paratrabecular spaces, progressing toward the interstitium as they mature. Megakaryocytes normally have a perisinusoidal distribution. Paratrabecular megakaryocyte growth signifies abnormal hematopoiesis.[23]

Megakaryocytic clustering is a diagnostic feature indicative of marrow regeneration after bone marrow transplantation or chemotherapy. This feature is also a hallmark of various neoplastic conditions, particularly myeloproliferative neoplasms like primary myelofibrosis (PMF), essential thrombocythemia (ET), and polycythemia vera (PV). Thus, this finding warrants further investigation.

Normal bone marrow contains few interstitial lymphocytes and occasional well-circumscribed reactive lymphoid aggregates in non-paratrabecular locations. However, neoplastic lymphoid aggregates exhibit features such as paratrabecular and perisinusoidal distribution, B-cell predominance and infiltration, and adipose tissue involvement (see Image. Paratrabecular Lymphoid Aggregate). Marrow samples with increased benign lymphoid aggregation have increased plasmacytosis and lipid granuloma formation. These findings may be associated with autoimmune conditions like rheumatoid arthritis.[24]

Diagnosing residual disease post-rituximab therapy becomes challenging due to resulting CD20 downregulation. PAX-5 and CD79a are alternative B-cell markers for evaluating residual disease following therapy.[25][26] Lymphoid aggregates may be present in MDS, myeloproliferative neoplasms, and lymphomatous marrow infiltration.

Lymphomatous bone marrow involvement can exhibit different patterns: focal (paratrabecular) pattern observed in follicular lymphomas and mantle cell lymphomas and non-paratrabecular pattern in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and Hodgkin lymphoma (HL). Diffuse solid and interstitial patterns are seen in aggressive and blastic lymphomas. Intravascular patterns are found in splenic marginal zone lymphoma and intrasinusoidal large cell lymphoma.[27] Studies indicate that 11.4% to 37% of B-cell lymphomas, 16% to 25% of T-cell lymphomas, and up to 11.8% of HL involve the bone marrow.[28][29] 

Mast cells are identifiable by their metachromatic granules, best visualized using Giemsa and toluidine-blue stains (see Image. Mast Cells). Atypical mast cells appear as spindle cells with a monocytoid nucleus, hypogranular cytoplasm, and paratrabecular location.

Increased mast cells in the marrow are observed in conditions such as aplastic anemia, CLL, hairy cell leukemia, impending blast crisis in chronic myeloid leukemia, systemic mastocytosis, mast cell sarcoma, and lymphoplasmacytic lymphoma. Neoplastic mast cells show aberrant CD25, CD30, and CD2 expression. Systemic mastocytosis is associated with an activating KITD816V mutation present in more than 90% of cases.[30]

Focal pathology detection

Neoplastic lymphoid aggregates, plasma cells, clusters of mast cells, and metastases can be focal processes. (see Image. Metastatic Carcinoma). Examining multiple tissue levels helps evaluate for focal pathology, especially when clinically indicated.

Nonhematopoietic malignancies that most commonly metastasize to the bone marrow originate from the breast, prostate, kidney, thyroid, and gastrointestinal tract.[31] To identify subtle tumor cell infiltration, a keratin stain is recommended in patients with a known epithelial cancer history and suspected bone metastases.

Dysplasia

Megakaryocytic dysplasia is often characterized by atypical megakaryocyte morphology and clustering and is best evaluated through trephine biopsies. In the normal marrow, megakaryocytes are usually found solitary in non-paratrabecular locations. However, megakaryocytes cluster in paratrabecular and perisinusoidal locations in myeloproliferative neoplasms and PMF but are more scattered in ET (see Image. Dysplastic Megakaryocytes).

A highly specific dysplastic MDS feature is micromegakaryocytosis, considered pathognomonic for this condition. Morphologically, ET megakaryocytes appear large with a staghorn-like nucleus, while those in PMF exhibit cloud-like, hypolobated nuclei with hyperchromasia and a decreased nuclear-cytoplasmic ratio (see Image. Primary Myelofibrosis).[32]

Overlapping clinicopathologic features among Philadelphia-negative myeloproliferative neoplasms (eg, PV, ET, and PMF) suggest a common JAK/STAT genetic pathway, with JAK2, CALR, and MPL being 3 of the most common driver mutations. Distinguishing PMF from PV and ET is crucial, as PMF is associated with a higher fibrosis incidence and acute leukemia progression. Bone marrow biopsy is critical in diagnosing and detecting leukemic transformation and fibrotic progression. Immunohistochemical stains such as CD34 are highly useful for determining blast counts, particularly in cases of marrow fibrosis.[33]

Fibrosis

Bone marrow fibrosis is a common cause of dry tap and contributes to discordances between aspirate and marrow findings. Fibrosis can arise from nonneoplastic conditions like bone marrow necrosis, metastatic nonhematopoietic malignancies, lymphoma infiltration, and myeloproliferative neoplasms, including PMF, post-ET, and PV.

Reticulin staining helps determine the extent of fibrosis in the marrow microenvironment, which is graded as follows:[34] 

• MF-0: Normal bone marrow with a scattered linear reticulin pattern but without intersections 
• MF-1: Loose reticulin network with numerous intersections, predominantly in perivascular regions 
• MF-2: Dense and diffuse increased reticulin with extensive intersections, occasionally interspersed with focal collagen bundles or focal osteosclerosis 
• MF-3: Dense and diffuse increased reticulin with extensive intersections, coarse collagen bundles, and significant osteosclerosis (see Image. Grade 3 Bone Marrow Fibrosis)

Necrosis

Bone marrow necrosis is a rare, potentially fatal complication that may arise from hematopoietic malignancies like myeloproliferative neoplasms, leukemias, lymphomas, and plasma cell myelomas. Chemotherapy and treatment with retinoic acid and granulocyte colony-stimulating factor increase the risk of bone marrow necrosis (see Image. Bone Marrow Necrosis). This condition can also occur after infections like parvovirus (especially in sickle cell patients) and HIV or the use of medications like sulfasalazine, interferon, and imatinib.[35] Distinguishing bone marrow necrosis from conditions like aplastic anemia, extensive amyloid deposition, and gelatinous transformation is vital to patient management.[36] 

Granulomas

Macrophage infiltration and granulomatous inflammation often pose diagnostic challenges. Exclusion of CD68-expressing mast cells mimicking granulomas is essential. Granulomas may be associated with diseases like HL but do not necessarily indicate direct lymphomatous bone marrow infiltration.[26]

Discordance Between Aspirate and Bone Marrow Trephine Biopsy

Discrepancies between the results of bone marrow aspirate and trephine biopsy samples occur frequently. Bone marrow aspirate criteria for the morphological assessment of blasts and erythroid or granulocytic dysplasia are more clearly defined than biopsy criteria. Focal lesions such as lymphoid and plasma cell aggregation, metastatic carcinomas, and dysplastic megakaryocyte growth can be underrepresented in aspirates and better appreciated on trephine biopsies. Dry marrow taps attributed to pathologies like myelofibrosis, aplastic anemia, and metastatic carcinoma infiltration are also better visualized on trephine biopsy.

Correlating BMA and BMB findings is crucial. The general guideline is that pathologies visible on the aspirate should also be identifiable on biopsies. However, the reverse may not always be accurate, emphasizing the importance of thorough clinicopathologic correlation in diagnosis.[26]

Bone Marrow Evaluation in Clonal Hematopoiesis 

Clonal hematopoiesis (CH) denotes the presence of cells arising from a mutated progenitor cell and exhibiting a propensity for proliferation in the absence of unexplained cytopenias, hematologic malignancies, or other clonal disorders.[11] The WHO 2022 has defined 2 categories:

• "Clonal hematopoiesis of indeterminate potential" (CHIP) refers to cases where CH with myeloid-malignancy-associated somatic gene mutations is observed at a variant allele fraction of more than 2%. Individuals with CHIP lack a diagnosed hematologic malignancy or unexplained cytopenia. The significance of a variant allele frequency (VAF) of less than 2% is currently unclear.

• "Clonal cytopenia of undetermined significance" (CCUS) refers to CH with at least 1 persistent cytopenia lasting longer than 4 months. These cytopenias are unexplained by any hematologic or systemic condition and do not meet the diagnostic criteria for defined myeloid malignancies. The peripheral blood criteria for CCUS, MDS, and MDS/MPN include the following:
• Hemoglobin less than 13 g/dL in male individuals and less than 12 g/dL in female individuals
• Absolute neutrophil count less than 1,800/mm³
• Platelet count less than 150,000/mm³

Bone marrow evaluation in CH requires a thorough understanding of the patient's clinical presentation and close collaboration between hematology and hematopathology teams. Excluding an underlying hematologic myeloid neoplasm requires an interprofessional approach.

Ancillary Studies

Ancillary bone marrow studies include immunohistochemistry, flow cytometry, cytogenetics, FISH, polymerase chain reaction (PCR), and next-generation sequencing (NGS). The upcoming sections delve into these studies’ substantial impact on patient management.

Clinical Significance

Molecular genetics have become pivotal for diagnosing, classifying, prognosticating, and treating hematopoietic malignancies. Certain neoplasms are now defined by molecular alterations, making molecular testing indispensable. Cytogenetics and FISH were traditionally used merely for chromosomal studies. Presently, NGS may be employed to detect significant somatic mutations.

Summarized below are the various hematopoietic conditions’ primary defining molecular pathways and mutations and their prognostic and clinical significance (see Table. Myeloproliferative, Eosinophilic, and Mast Cell Neoplasms).[37][38]

Table 3. Myeloproliferative, Eosinophilic, and Mast Cell Neoplasms

Table 4. Myelodysplastic neoplasms and MDS/MPNs

The prognosis of various genetically defined AMLs has been stated above (see Table 1. Features of Genetically Defined AML). Optimizing treatment strategies requires identifying targetable mutations like FLT3-ITD, IDH-1, and IDH2 by techniques such as PCR or capillary electrophoresis. AML cases with TP53 mutation, specifically with a VAF exceeding 10%, are now denoted as "AML with mutated TP53." The mutation is associated with an unfavorable prognosis despite aggressive therapeutic interventions.[10] 

Posttreatment minimal residual disease (MRD) monitoring identifies impending relapse and facilitates early interventions. Multiparameter flow cytometry and molecular techniques like PCR and NGS can now be performed on peripheral blood and bone marrow samples. Notably, bone marrow samples offer higher sensitivity in MRD evaluation.

NGS can provide information about preleukemic clones like DNMT3A, TET2, and ASXL1. These mutations may not be detectable during initial diagnosis but could become apparent through NGS. Importantly, the presence of these mutations does not necessarily predict disease relapse. Meanwhile, mutations like NPM1, RUNX1::RUNX1T1, and CBFB::MYH11 are usually present at diagnosis and persist through relapse. Mutations like FLT3-ITD, NRAS, and KRAS may exhibit outcome variability following therapeutic interventions.[37]

Acute lymphoid leukemia subtypes are also defined based on molecular genetics in the WHO 2022 classification. Cytogenetics and FISH are efficient diagnostic tools for identifying the defining chromosomal alterations (eg, BCR::ABL1, KMT2A::AFF1, ETVG::RUNX1, TCF3::PBX1, and iAMP21), and prognostic factors like aneuploidy.[37]

The ICSH and CAP advocate formulating an “Integrated Diagnosis,” which combines analysis of the peripheral blood, bone marrow aspirate, and trephine biopsy with ancillary and molecular testing. An integrated diagnosis aims to classify hematopoietic neoplasms as currently defined by the WHO and provide hematologists with pertinent information to help determine management. These insights are instrumental in devising tailored and effective therapeutic strategies and optimizing overall treatment outcomes.

The information that must be included in a comprehensive bone marrow examination report are the following:

• Institutional Information
  • Institution’s name 
• Patient Details
  • Patient's name
  • Birth date
  • Medical record number
• Requesting Physician
  • Physician’s name
  • Medical license number
• Procedure Details
  • Procedure date
  • Indication for bone marrow examination
  • Procedure type (aspirate, trephine biopsy)
  • Procedure site (iliac crest, sternum, etc)
• Peripheral Blood Smear
  • CBC parameters
  • Peripheral blood smear description
• Bone Marrow Aspirate Examination
  • Morphologic findings: cellularity, nucleated differential cell count, myeloid: erythroid ratio, blast percentages, erythropoiesis, myelopoiesis, megakaryocytes, lymphocytes, plasma cells, other hematopoietic cells, abnormal cells
  • Special stains: iron stain, cytochemistry
  • Other investigations: cytogenetics, FISH, PCR, and molecular methods, including NGS
  • Flow cytometry results (if performed)
• Bone Marrow Trephine Biopsy Examination
  • Morphologic findings: length of core biopsy, cellularity, bone architecture, location, number, morphology, and maturation of erythroid, myeloid and megakaryocyte lineages, plasma cells, lymphocytes, and macrophages; abnormal cells or infiltrates.
  • Special stains: Reticulin stain
  • Immunohistochemistry results
• Final Integrated Diagnosis per WHO Criteria
  • Summary of findings
• Note
• Signature and date of reporting

Enhancing Healthcare Team Outcomes

Bone marrow examination is an indispensable tool in the diagnosis and posttreatment monitoring of hematopoietic conditions. Developing a systematic bone marrow evaluation approach and establishing a standardized reporting methodology, including molecular studies, is essential. These practices help promote a better understanding of the terminology and behavior of hematopoietic neoplasms, thus fostering efficient collaboration within interprofessional teams caring for patients with hematopoietic disorders.

The interprofessional team members in these cases include pathologists, hematologists, oncologists, primary care physicians, nurses, and pharmacists. Pathologists provide accurate diagnostic assessments based on bone marrow samples. Hematologists oversee patient management and treatment strategies tailored to specific blood disorders. Oncologists administer specialized cancer care, including chemotherapy regimens.

Primary care physicians coordinate overall patient care and ensure continuity beyond specialty settings. Nurses and pharmacists support patient care, administer treatments, and manage side effects. Laboratory analysts process and evaluate bone marrow samples, contributing to accurate diagnostic reports. Together, these healthcare professionals ensure comprehensive care and optimal treatment outcomes for patients undergoing bone marrow examination.